1. Field of the Invention
This invention relates generally to the fields of immunology and medicine and more specifically to methods for providing immunoprotection against HIV-1 infection.
2. Background Information
The incidence of acquired immunodeficiency syndrome (AIDS) has reached an epidemic level, particularly in third world countries in Africa, Asia and the Caribbean. Despite the expenditure of billions of dollars for research to discover drugs to treat or cure the disease, however, only modest progress has been made in identifying drugs that can delay the progress of the disease.
The causative agent of AIDS is the human immunodeficiency virus (HIV-1). HIV-1 infects a particular cell type of the immune system, the T cell. Upon entering a T cell, the HIV-1 genomic DNA is incorporated into the T cell genome, where it directs synthesis of viral proteins. New copies of the HIV-1 virus then are released from the infected T cell and further infect additional T cells. Ultimately, the infected T cells die and the HIV-1 infected individual's immune system becomes depleted and cannot ward off subsequent infections. As a result, victims of AIDS typically die from infections that normally would cause, at worst, a mild illness in a healthy individual.
Initially, treatments for AIDS were limited to methods of treating the infections that resulted from the depleted immune response. Later, drugs such as AZT and ddI, which are known as nucleoside analogs, were identified that could interfere with replication of the HIV-1 DNA. These drugs, particularly in combination, can prolong the life of AIDS patients. More recently, a class of drugs called protease inhibitors have been reported to be even more effective in inhibiting HIV-1 replication. It is hoped that the protease inhibitors, perhaps in combination with the nucleoside analogs, will further prolong the life of AIDS patients and even result in cures.
While the use of drugs as described above provides a means to kill the virus in HIV-1 infected individuals, such drugs are useful only after a person has become infected; they have no enhancing effect on the immune system. Clearly, a more preferable approach to stifling the AIDS epidemic would be to prevent HIV-1 infection in the first place. Vaccines, which stimulate a person's immune response against the vaccinating agent, are the logical choice for preventing HIV-1 infection. For example, vaccines have been used to prevent or reduce the severity of various viral diseases, including polio, measles, smallpox and influenza. In addition, a vaccine can stimulate the immune system in individuals already infected with a virus.
Numerous approaches have been made to develop a vaccine that would increase a person's resistance to infection with the AIDS virus. However, while various types of HIV-1 vaccines have been designed and have been tested in clinical trials, each suffers from a serious limitation. For example, vaccines composed of portions of an HIV-1 protein or using a killed HIV-1 virus have been produced. However, HIV-1 does not have a stable structure, but changes its identity rapidly as it reproduces. As a result, an immune response that is stimulated against a particular HIV-1 protein or strain of HIV-1 is ineffective against a changed form of the virus. Furthermore, portions of the HIV-1 surface proteins that potentially would be most effective in a vaccine, in fact stimulate the production of antibodies that facilitate HIV-1 infection.
Attenuated vaccines, which consist of live but reproductively defective viruses, also have been proposed. However, there is justified concern for injecting such an HIV-1 virus into an individual, particularly an otherwise healthy person. Thus, a need exists for a vaccine that provides a broad based immune response against HIV-1 but does not carry the attendant risks and limitations associated with the use of HIV-1 as the vaccinating agent. The present invention satisfies this need and provides additional advantages.